T cell receptor-mediated signs and signals governing T cell development

The developmental fate of T cells is largely controlled by the nature and s uccess of signals mediated by the pre-T cell receptor (TCR) and TCR complex es. These intracellular signals are regulated by cascades of protein tyrosi ne phosphorylations initiated following ligand binding to the pre-TCR or TC R complexes. The phosphorylation cascades are primarily orchestrated by two distinct families of protein tyrosine Kinases (PTKs), the Src- and the Syk /ZAP-70-families. Germline gene targeting experiments, several human immuno deficiencies and somatic cell mutants have all contributed to our understan ding of how these families of kinases coordinate their actions to promote s ignaling. Upon activation, the PTKs transmit their signals to a number of n ewly described adaptor proteins including LAT, SLP-76, and vav, among other s. The folio-wing review combines results derived from different experiment al strategies to examine the contributions of the PTKs and the adaptor mole cules to pre-TCR and TCR signaling processes.